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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) is a key regulator of energy homeostasis and is implicated in the development of obesity and type 2 diabetes. Whereas it is known that hypothalamic administration of exogenous NPY peptides leads to increased body weight gain, hyperphagia, and many hormonal and metabolic changes characteristic of an obesity syndrome, the Y receptor(s) mediating these effects is disputed and unclear. To investigate the role of different Y receptors in the NPY-induced obesity syndrome, we used recombinant adeno-associated viral vector to overexpress NPY in mice deficient of selective single or multiple Y receptors (including Y1, Y2, and Y4). Results from this study demonstrated that long-term hypothalamic overexpression of NPY lead to marked hyperphagia, hypogonadism, body weight gain, enhanced adipose tissue accumulation, hyperinsulinemia, and other hormonal changes characteristic of an obesity syndrome. NPY-induced hyperphagia, hypogonadism, and obesity syndrome persisted in all genotypes studied (Y1(-/-), Y2(-/-), Y2Y4(-/-), and Y1Y2Y4(-/-) mice). However, triple deletion of Y1, Y2, and Y4 receptors prevented NPY-induced hyperinsulinemia. These findings suggest that Y1, Y2, and Y4 receptors under this condition are not crucially involved in NPY's hyperphagic, hypogonadal, and obesogenic effects, but they are responsible for the central regulation of circulating insulin levels by NPY.
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PMID:Combined deletion of Y1, Y2, and Y4 receptors prevents hypothalamic neuropeptide Y overexpression-induced hyperinsulinemia despite persistence of hyperphagia and obesity. 1687 43

With the worldwide epidemic of metabolic syndrome (MetS), the proportion of women that are overweight/obese and overfed during pregnancy has increased. The resulting abnormal uterine environment may have deleterious effects on fetal metabolic programming and lead to MetS in adulthood. A balanced/restricted diet and/or physical exercise often improve metabolic abnormalities in individuals with obesity and type 2 diabetes mellitus (T2D). We investigated whether reducing fat intake during the periconceptual/gestation/lactation period in mothers with high-fat diet (HFD)-induced obesity could be used to modify fetal/neonatal MetS programming positively, thereby preventing MetS. First generation (F1) C57BL/6J female mice with HFD-induced obesity and T2D were crossed with F1 males on control diet (CD). These F1 females were switched to a CD during the periconceptual/gestation/lactation period. At weaning, both male and female second generation (F2) mice were fed a HFD. Weight, caloric intake, lipid parameters, glucose, and insulin sensitivity were assessed. Sensitivity/resistance to the HFD differed significantly between generations and sexes. A similar proportion of the F1 and F2 males (80%) developed hyperphagia, obesity, and T2D. In contrast, a significantly higher proportion of the F2 females (43%) than of the previous F1 generation (17%) were resistant (P<0.01). Despite having free access to the HFD, these female mice were no longer hyperphagic and remained lean, with normal insulin sensitivity and glycemia but mild hypercholesterolemia and glucose intolerance, thus displaying a "satiety phenotype." This suggests that an appropriate dietary fatty acid profile and intake during the periconceptual/gestation/lactation period helps the female offspring to cope with deleterious intrauterine conditions.
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PMID:Resistance to high-fat diet in the female progeny of obese mice fed a control diet during the periconceptual, gestation, and lactation periods. 1716 37

Pediatric obesity is increasing worldwide and disproportionately affects the economically and socially disadvantaged. Obese children are at risk of developing the (dys)metabolic syndrome, insulin resistance, early-onset type 2 diabetes mellitus, polycystic ovarian syndrome, hypertension, hyperlipidemia, and obstructive sleep apnoea. Those with diabetes may have mixed features of type 1 and type 2 diabetes mellitus. Pediatric obesity is the result of persistent adverse changes in food intake, lifestyle, and energy expenditure. It may be because of underlying a genetic syndrome or a conduct disorder. Children living in urban settings often lack safe, affordable, and accessible recreational facilities. Tight educational schedules mean less free time, while computer games and television have become preferred recreational activities. More families are eating out or eating take-out meals and processed foods at home because of pressures of work and time constraints. Consumer advertising targeted at children and the ready availability of vending machines encourage unwise food choices. Some children eat excessively because they are depressed, anxious, sad, or lonely. Often families and obese children are aware of the need for healthy eating and exercise but are unable to translate knowledge into weight loss. Population-based measures such as public education, school meal reforms, child-safe exercise friendly environments, and school-based and community-based exercise programs have been shown to be successful to varying degrees, but there remain individuals who will need special help to overcome obesity. Overeating (e.g. binge eating) may be a manifestation of disordered coping behavior but may also be because of defects in the neural and hormonal control of appetite and satiety. New pharmacological approaches are targeting these areas. We need a coordinated approach involving government, communities, and healthcare providers to provide a continuum of population-based interventions, focused screening, and personalized multidisciplinary interventions for the obese child and family.
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PMID:An overview of pediatric obesity. 1799 Nov 36

Brain melanocortin system (MC-system) participates in regulation of energy homeostasis. Dominant mutation yellow of the Agouti gene leads to the hyperphagia, obesity and type 2 diabetes. Stress is known to inhibit food intake and body weight. The aim of the work was to study effects of repeating emotional stress on food intake and lipid-carbohydrate metabolism in Ay-mice. Male mice of C57B1/6J strain predisposed to the obesity (Ay/a-genotype) and normal (a/a-genotype) were used. In control group food intake, body weight and blood levels of insulin and leptin were increased in Ay/a-mice as compared to a/a-mice. Repeating emotional stress (30 min restraint 3 times a week for 5 weeks) did not alter food intake and indices of lipid-carbohydrate metabolism in a/a-mice and decreased food intake, body weight and blood levels of insulin and leptin in Ay/a-mice. Insulin and leptin blood levels were the same in Ay/a- and a/a-mice on 5 week of treatment. The stress increased basal and stress-induced concentrations of corticosterone to an equal degree in Ay/a- and a/a-mice. Thus, light repeating emotional stress hampered development of obesity and 2 type diabetes in the mice with the Agouti yellow mutation.
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PMID:[Repeating of emotional stress prevents development of melanocortin obesity and type 2 diabetes in the mice with the Agouti yellow mutation]. 1819 91

An epidemic of overweight/obesity and type 2 diabetes, caused by overeating nutrient-poor energy-dense foods and a sedentary lifestyle, is spreading rapidly throughout the world. Abdominal obesity represents a serious threat to health because it increases the risk of developing many chronic diseases, including cardiovascular disease and cancer. Calorie restriction (CR) with adequate nutrition improves cardiometabolic health, prevents tumorigenesis and increases life span in experimental animals. The purpose of this review is to evaluate the metabolic and clinical implications of CR with adequate nutrition in humans, within the context of data obtained in animal models. It is unlikely that information regarding the effect of CR on maximal life span in humans will become available in the foreseeable future. In young and middle-aged healthy individuals, however, CR causes many of the same cardiometabolic adaptations that occur in long-lived CR rodents, including decreased metabolic, hormonal and inflammatory risk factors for diabetes, hypertension, cardiovascular disease and cancer. Unraveling the mechanisms that link calorie intake and body composition with metabolism and aging will be a major step in understanding the age-dependency of a wide range of human diseases and will also contribute to improve the general quality of life at old ages.
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PMID:Calorie restriction and cardiometabolic health. 1827 79

Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity occurs in type 2 diabetes, and stress is assumed to play a causal role. However, intermittent restraint stress, a model mimicking some mild stressors, delays development of hyperglycemia in Zucker diabetic fatty (ZDF) rats. We examine whether such stress delays hyperglycemia independent of stress-induced reductions in hyperphagia and is due to adaptations in gene expression of HPA-related peptides and receptors that ameliorate corticosteronemia and thus hyperglycemia. ZDF rats were intermittently restraint stressed (1 h/d, 5 d/wk) for 13 wk and compared with obese control, pair fed, and lean ZDF rats. After 13 wk, basal hormones were repeatedly measured over 24 h, and HPA-related gene expression was assessed by in situ hybridization. Although restraint initially induced hyperglycemia, this response habituated over time, and intermittent restraint delayed hyperglycemia. This delay was partly related to 5-15% decreased hyperphagia, which was not accompanied by decreased arcuate nucleus NPY or increased POMC mRNA expression, although expression was altered by obesity. Obese rats demonstrated basal hypercorticosteronemia and greater corticosterone responses to food/water removal. Basal hypercorticosteronemia was further exacerbated after 13 wk of pair feeding during the nadir. Importantly, intermittent restraint further delayed hyperglycemia independent of food intake, because glycemia was 30-40% lower than after 13 wk of pair feeding. This may be mediated by increased hippocampal MR mRNA, reduced anterior pituitary POMC mRNA levels, and lower adrenal sensitivity to ACTH, thus preventing basal and stress-induced hypercorticosteronemia. In contrast, 24-h catecholamines were unaltered. Thus, rather than playing a causal role, intermittent stress delayed deteriorations in glycemia and ameliorated HPA hyperactivity in the ZDF rat.
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PMID:Adaptation to mild, intermittent stress delays development of hyperglycemia in the Zucker diabetic Fatty rat independent of food intake: role of habituation of the hypothalamic-pituitary-adrenal axis. 1832 96

Prion diseases are fatal neurodegenerative diseases that can induce endocrinopathies. The basis of altered endocrine function in prion diseases is not well understood, and the purpose of this study was to investigate the spatiotemporal relationship between energy homeostasis and prion infection in hamsters inoculated with either the 139H strain of scrapie agent, which induces preclinical weight gain, or the HY strain of transmissible mink encephalopathy (TME), which induces clinical weight loss. Temporal changes in body weight, feed, and water intake were measured as well as both non-fasted and fasted concentrations of serum glucose, insulin, glucagon, beta-ketones, and leptin. In 139H scrapie-infected hamsters, polydipsia, hyperphagia, non-fasted hyperinsulinemia with hyperglycemia, and fasted hyperleptinemia were found at preclinical stages and are consistent with an anabolic syndrome that has similarities to type II diabetes mellitus and/or metabolic syndrome X. In HY TME-infected hamsters, hypodipsia, hypersecretion of glucagon (in both non-fasted and fasted states), increased fasted beta-ketones, fasted hypoglycemia, and suppressed non-fasted leptin concentrations were found while feed intake was normal. These findings suggest a severe catabolic syndrome in HY TME infection mediated by chronic increases in glucagon secretion. In both models, alterations of pancreatic endocrine function were not associated with PrP(Sc) deposition in the pancreas. The results indicate that prominent endocrinopathy underlies alterations in body weight, pancreatic endocrine function, and intake of food. The prion-induced alterations of energy homeostasis in 139H scrapie- or HY TME-infected hamsters could occur within areas of the hypothalamus that control food satiety and/or within autonomic centers that provide neural outflow to the pancreas.
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PMID:Prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases. 1843 55

Diabetes mellitus has been defined as a "group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both" and encompasses a wide range of heterogeneous conditions. Common type 2 diabetes mellitus (T2DM) results from a combination of genetic and acquired factors. However, lifestyle factors, particularly overeating and physical inactivity, are the major clinical determinants of T2DM. Insulin resistance is a common feature of T2DM, but it is unlikely to cause T2DM unless progressive loss of beta-cell function develops. Significant reduction in beta-cell function is already present at the time of T2DM diagnosis, and it continuously declines irrespective of treatment. As such, the progressive loss of beta-cell function dictates the rate of worsened glycemic control. Development of progressive deterioration accelerates via gluco- and lipotoxicity, loss of beta-cell function, and shrinkage of beta-cell mass. Understanding the causes for beta-cell failure is therefore of capital importance to develop new and more effective therapeutic strategies.
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PMID:Beta-cell failure in type 2 diabetes mellitus. 1862 13

The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention, and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with Zucker diabetic fatty-lean rats that have a defect in pancreatic beta-cell function but normal leptin signaling. We have characterized the model with respect to diabetes incidence; age of onset; longitudinal measurements of glucose, insulin, and lipids; and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations >250 and >450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of beta-cell decompensation. The incidence of diabetes in male and female rats was 92 and 43%, respectively, with an average age of onset of 6 mo in males and 9.5 mo in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry, and islet insulin content further support a role for beta-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus diabetes in the UC Davis-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment, and prevention of T2DM.
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PMID:Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat. 1883 86

The genetic model of diabetes mellitus was studied on mutant C57Bl/KsLepr(db/+) mice. These mice were characterized by high concentrations of glucose and glycosylated hemoglobin in the blood, polyuria, polyphagia, polydipsia, progressive obesity, biphasic morphological changes in insular islets of the pancreas (hyperplasia and atrophy), fatty degeneration of the liver, and hypoplasia of the spleen tissue and lymph nodes. Our results indicate that C57Bl/KsLepr(db/+) mice serve as an adequate model of type 2 diabetes mellitus. This model is suitable for testing of therapeutic methods for type 2 diabetes mellitus.
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PMID:Mutant C57Bl/Kslepr(db/+) mice as a genetic model of type 2 diabetes mellitus. 1885 8


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